ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.

ECFS standards of care on CFTR-related disorders: Towards a comprehensive program for affected individuals.

After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.

Can introducing a direct endocrine pathway reduce hyponatraemia in elective knee and hip replacements? A closed-loop audit and service evaluation study.

INTRODUCTION: Hyponatraemia has a prevalence of up to 30% after orthopaedic surgery and is associated with poor outcomes, including around 20% mortality and longer hospital stays. This study assessed the prevalence of hyponatraemia following total hip and knee replacement, the causes, further tests, management, effect on length of stay, intensive care admissions and the impact of an endocrinology hyponatraemia protocol. MATERIALS AND METHODS: Day one postoperative urea and electrolyte results for patients undergoing elective total hip and knee replacements were reviewed. Retrospective data was gathered through the web-based requesting and reporting system ICE. Parameters included demographics, procedure, sodium pre- and postoperatively, endocrine input, high-dependency admissions and length of hospital stay. Next, a hyponatraemia protocol based on NICE guidance was developed with the endocrinology department and a second audit cycle was initiated. SPSS software was used to analyse the data. RESULTS: Hyponatraemia occurred in 12% of patients, resulted in a significantly longer stay (7.7 days vs 4.6, t -4.6, p < 0.00001) and multiple critical care admissions (8 days). It was more common in total knee replacement (chi square 5.5194, p = 0.018807) and older age (t -2.81083, p = 0.002619). Prior to implementation of the endocrine pathway, hyponatraemia was under-investigated (38%). The precipitating factors such as age and use of diuretics corroborated with prior research. Implementation of the hyponatraemia protocol resulted in quicker endocrinology referrals (2.3 vs 3.6 days), reduced length of stay by 0.7 days (t -2.40973, p = 0.008144) and reduced intensive care days to 0 (chi square 4.6189, p = 0.031622). DISCUSSION: This study found a similar incidence of hyponatremia as earlier research with the same precipitating factors, the only exception being an increased incidence in patients undergoing knee compared with hip replacemenr The introduction of the direct endocrine pathway proved to be safe and effective without increasing local workload significantly. The main limitation in this project was the fact that it was carried out in a single unit, although this process could be easily replicated should other units wish to adopt it and compare results over a wider cohort. CONCLUSIONS: This endocrine pathway is easily reproducible for other departments. It may help reduce waiting times and improve outcomes for total hip and knee replacements within the NHS.

Well-being and mental stress in the population study of women in Gothenburg, Sweden: cohort comparisons from 1980 to 2016 of 36-year trends and socioeconomic disparities in 38-and 50-year old women.

BACKGROUND: Women's lives have dramatically changed in recent decades as evidenced by trends in educational attainment, employment outside the home, income, and other socioeconomic factors. Self-reported health in 18-70 year old women has been reported to be significantly lower than in men. In Sweden, the 2005 National Public Health Report showed that stressful work environments have become more common, especially for women. The purpose of the study was to monitor trends in well-being and perceived mental stress in the populations of 38- and 50-year-old women and to examine associations with socioeconomic position (SEP). SUBJECTS: In 1980, 2004, and 2017, population-based samples of 38- and 50-year old women were recruited into the Prospective Population Study of Women in Gothenburg (PPSWG), Sweden. This population-based study included participants from selected birth cohorts to participate in health examinations, at similar ages and with similar protocols on each occasion. METHODS: Birth cohort comparisons between three representative samples of 38- and 50-year-old women. Well-being (scale 1-7) and perceived mental stress (scale 1-6) based on questionnaires were the main outcomes studied in relation to time. Socioeconomic position (SEP) based on socio-occupational group, i.e. occupational and educational level combined, were examined as correlates of well-being and mental stress at different points in time. RESULTS: Perception of good well-being increased in generations of 50-year-old women between 1980 to 2016, but no significant time trends were seen in 38-year-old women. Perception of high mental stress increased between 1980 and 2016, for both 38-and 50-year-old women. Belonging to a low socio-occupational group was associated with lower perceived well-being in 1980 but not in 2016. Belonging to a low socio-occupational group was not associated with perceived mental stress at any examination. CONCLUSIONS: Contemporary women of today have generally higher perceptions of well-being but also higher mental stress regardless of belonging to low or high socio-occupational group. Associations between poor well-being and belonging to a low socio-occupational group that were observed in 1980 and 2004 were not observed in 2016. The Prospective Population Study of Women in Gothenburg, Sweden was approved by the ethics committee of University of Gothenburg (Dnr 65-80; Ö564-03; 258-16). The studies comply with the Declaration of Helsinki and informed consent has been obtained from the subjects.

Self-reported pain or injury from equipment used on military deployment.

BACKGROUND: Information about pain and injury from equipment on a particular deployment is not disaggregated in the literature; thus, the nature of the issue is unclear. AIMS: To determine the prevalence of pain or injury during a particular deployment that military personnel attributed to equipment they used on this deployment; and to document the types of equipment they identified, the type of pain or injury and how they thought the pain or injury occurred. METHODS: This paper analyses data from a deployment and health survey of Australian Defence Force personnel. The participants are 8932 personnel who deployed to Iraq and 6534 who deployed to Afghanistan. Participants indicated whether they experienced pain or injury from equipment they used on deployment and detailed their experiences in response to an open-ended question (n = 563). RESULTS: Sixteen per cent of Iraq-deployed and 21% of Afghanistan-deployed participants reported pain or injury from equipment they used on deployment. Body armour was the most common equipment identified; however, a wide range of equipment was related to pain or injury. A new finding is that pain or injury related to armour was attributed to its wear in vehicles and during vehicle ingress or egress. CONCLUSIONS: Knowledge of the nature of pain or injury related to equipment used on deployment may help inform improved designs and practices to reduce or prevent avoidable harm to serving personnel.

Duration of estrogen exposure during reproductive years, age at menarche and age at menopause, and risk of cardiovascular disease events, all-cause and cardiovascular mortality: a systematic review and meta-analysis.

BACKGROUND: Little is known about the estrogen exposure measurement and mutual effect of age at menarche and age at menopause in the risk of cardiovascular disease (CVD) events. OBJECTIVES: To evaluate estrogen exposure measurement and describe mutual effect of age at menarche and age at menopause in the risk of CVD events. SEARCH STRATEGY: Systematic review of literature in PubMed, Embase and Web of Science for studies published up to 28 June 2020. SELECTION CRITERIA: Observational studies related to estrogen exposure measurement, including mutual effect of age at menarche and age at menopause and risk of CVD events. DATA COLLECTION AND ANALYSIS: Synthesis of evidence was conducted by reviewing individual estimates, followed by meta-analysis. The study received no external funding. MAIN RESULTS: A total of 75 studies were included in synthesis of evidence, of which 17 studies were included in meta-analysis. Reproductive lifespan (age at menopause - age at menarche), endogenous estrogen exposure and total estrogen exposure were used for estrogen exposure measurement. Reproductive lifespan was by far the most commonly used method for estrogen exposure measurement. A shorter reproductive lifespan was associated with a higher risk of CVD events; the pooled relative risk (95% CI) was 1.31 (1.25-1.36) for stroke events. Robust epidemiological studies with measurement of estrogen exposure and associated health risk would strengthen the evidence. CONCLUSIONS: Reproductive lifespan was the most commonly used method for estrogen exposure measurement in epidemiological studies. A shorter reproductive lifespan was associated with a higher risk of CVD events, particularly stroke. TWEETABLE ABSTRACT: A systematic review and meta-analysis found that women with a shorter reproductive lifespan have a higher risk of stroke events.

A pro-inflammatory diet is associated with increased risk of developing hypertension among middle-aged women.

BACKGROUND AND AIMS: A pro-inflammatory diet is thought to lead to hypertension through oxidative stress and vessel wall inflammation. We therefore investigated the association between the dietary inflammatory index (DII) and developing hypertension in a population-based cohort of middle-aged women. METHODS AND RESULTS: The Australian Longitudinal Study on Women's Health included 7169 Australian women, aged 52 years (SD 1 year) at baseline in 2001, who were followed up through 4 surveys until 2013. The DII, a literature-derived dietary index that has been validated against several inflammatory markers, was calculated based on data collected via a validated food-frequency questionnaire administered at baseline. Hypertension was defined as new onset of doctor-diagnosed hypertension, ascertained through self-report between 2001 and 2013. Generalised Estimating Equation analyses were used to investigate the association between the DII and incident hypertension. The analyses were adjusted for demographic and hypertension risk factors. During 12-years follow-up we identified 1680 incident cases of hypertension. A more pro-inflammatory diet was associated with higher risk of hypertension in dichotomised analyses with an ORfully adjusted of 1.24, 95% CI: 1.06-1.45. CONCLUSION: A pro-inflammatory diet might lead to a higher risk of developing hypertension. These results need to be replicated in other studies.

Ten Year Experience of Radioiodine Dosimetry: is it Useful in the Management of Metastatic Differentiated Thyroid Cancer?

AIMS: When a fixed activity of radioiodine is given for differentiated thyroid cancer (DTC), absorbed doses of radioiodine can vary widely and are not usually measured. Leeds Cancer Centre has routinely used a form of lesion-specific dosimetry for radioiodine patients. This study investigated if the results of dosimetry influenced treatment decisions for patients with advanced DTC. MATERIALS AND METHODS: Since 2005, patients with regionally advanced/metastatic DTC, who underwent radioiodine treatment together with dosimetry, were included in this study. Patients were excluded if their radioiodine post-treatment scan showed no abnormal uptake. Dosimetry was calculated using images taken 2, 3 and 7 days post-radioiodine. Regions of interest were drawn around lesions that required dosimetry and a time-dose activity curve was created. The total cumulative activity was equal to the area under the curve. Each patient's results were prospectively assessed by their oncologist regarding the usefulness of dosimetry in making management decisions. RESULTS: Thirty patients were studied and underwent 102 admissions of radioiodine between them. Dosimetry was carried out during 83 of 102 admissions. An absorbed dose of >20 Gy was taken as significant from dosimetry calculations, following which further radioiodine was considered. In 80% of patients, dosimetry was found to be useful when making treatment decisions. Only on 1/19 admissions did dosimetry calculate a minimum dose above 20 Gy in patients who had a total of four or more admissions for radioiodine. Ten per cent (3/30) had a complete response to radioiodine, both biochemically and radiologically, with a median follow-up of 6.7 months. Thirty-three per cent had a partial response/stable disease to radioiodine. The remainder had progressive disease. The decision to discontinue radioiodine therapy was often based on dosimetry and thyroglobulin results. Dosimetry was very useful for patients with thyroglobulin antibodies. CONCLUSION: Only 10% had a complete response. Therefore, a significant number of patients became refractory to radioiodine during a course of repeat admissions for treatment. Dosimetry (often together with thyroglobulin and anatomical scans) helped to identify these patients to avoid further futile radioiodine therapy.

Characteristics of Queensland physicians and the influence of rural exposure on practice location.

The Queensland branch of the Royal Australasian College of Physicians (RACP) commissioned this study to update their workforce profile and examine rural practice. The present investigation aimed to describe characteristics of Queensland physicians and determine the influence of childhood and training locations on current rural practice. A cross-sectional online survey, conducted 4 July-4 November 2013, was administered to Fellows of The RACP, Queensland. Descriptive statistics report characteristics and logistic regression analyses identify associations and interactions. The outcome measure was current practice location using the Australian Standard Geographic Classification - Remoteness Area. Data were obtained for 633 physicians. Their average age was 49.5 years, a third was female and a quarter was in rural practice. Rural practice was associated with a rural childhood (odds ratio (OR) (95% confidence interval, CI) 1.89 (1.10, 3.27) P = 0.02) and any time spent as an intern (OR 4.07 (2.12, 7.82) P < 0.001) or registrar (OR 4.00 (2.21, 7.26) P < 0.001) in a rural location. Physicians with a rural childhood and rural training were most likely to be in rural practice. However, those who had a metropolitan childhood and a rural internship were approximately five times more likely to be working in rural practice than physicians with no rural exposure (OR 5.33 (1.61, 17.60) P < 0.01). The findings demonstrate the positive effect of rural vocational training on rural practice. A prospective study would determine if recent changes to the Basic Physician Training Pathway and the Basic Paediatric Training Network (more rural training than previous pathways) increases the rate of rural practice.

Enhanced risk of illness during the 1918 influenza pandemic after previous influenza-like illnesses in three military populations.

The reasons for the unprecedented mortality during the 1918 influenza pandemic remain poorly understood. We examined morbidity records from three military cohorts from years prior to and during the 1918 pandemic period to assess the effects of previous respiratory illnesses on experiences during the pandemic. Clinical registers and morbidity lists were examined to identify all medical encounters for acute respiratory illnesses in students at two U.S. military officer training academies and Australian soldiers deployed in Europe. Influenza-like illness prior to the major pandemic wave of 1918 predisposed Australian soldiers [relative risk (RR) 1·37, 95% confidence interval (CI) 1·18-1·60, P < 0·0001] and US officer trainees at West Point (RR 3·10, 95% CI 2·13-4·52, P < 0·0001) and Annapolis (RR 2·03, 95% CI 1·65-2·50, P < 0·0001) to increased risks of medically treated illnesses in late 1918. The findings suggest that susceptibility to and/or clinical expressions of the 1918 pandemic influenza virus depended on previous experiences with respiratory infectious agents. The findings are consistent with observations during the 2009 pandemic in Canada and may reflect antibody-dependent enhancement of influenza infection.

Unit cohesion, traumatic exposure and mental health of military personnel.

BACKGROUND: The benefit of military unit cohesion to morale and psychological resilience is well established. But it remains unclear whether unit cohesion modifies the association between deployment-related traumatic exposure and mental health problems. AIMS: To examine the association between unit cohesion, traumatic exposure and poor mental health [symptoms of post-traumatic stress disorder (PTSD), psychological distress and alcohol dependency] and assess whether the relationship between traumatic exposure and poor mental health differs by level of unit cohesion. METHODS: A self-reported cross-sectional survey of Australian military personnel deployed to Iraq or Afghanistan between 2001 and 2009. RESULTS: Among 11411 participants, those with low levels of unit cohesion had higher odds of PTSD symptoms [aOR (95% CI): 2.54 (1.88, 3.42)], very high psychological distress [aOR (95% CI): 4.28 (3.04, 6.02)] and a high level of alcohol problems [aOR (95% CI): 1.71 (1.32, 2.22)] compared with those reporting high unit cohesion on deployment. Higher exposure to traumatic events on deployment was associated with greater risk of PTSD symptoms, very high levels of psychological distress and high levels of alcohol problems in this cohort. However, there was no evidence of a statistically significant interaction between unit cohesion and traumatic exposures in influencing poor mental health. CONCLUSIONS: Our findings suggest that both unit cohesion and traumatic exposure are independently associated with poor mental health. Efforts to improve military unit cohesion may help to improve the mental health resilience of military personnel, regardless of their level of traumatic exposure.

Factors associated with low unit cohesion in Australian Defence Force members who deployed to the Middle East (2001-2009).

INTRODUCTION: Unit cohesion has been shown to bolster the mental health of military personnel; hence, it is important to identify the characteristics that are associated with low unit cohesion, so that interventions to improve unit cohesion can be targeted and implemented. Little is known about the factors associated with low unit cohesion. This research aims to identify demographic, military service and deployment factors associated with low unit cohesion. METHODS: Data from a self-reported cross-sectional study of 11 411 current or ex-serving Australian military personnel deployed to Iraq or Afghanistan between 2001 and 2009 were used. Multivariable logistic regression was used to investigate the research aims. RESULTS: Being female (adjusted OR (aOR) (95% CI) 1.35 (1.21 to 1.51)), non-commissioned officer (aOR (95% CI) 1.50 (1.39 to 1.62)), lower ranked (aOR (95% CI) 1.74 (1.51 to 2.01)) or having left military service (aOR (95% CI) 1.71 (1.46 to 2.02)) was associated with reporting low unit cohesion. Potentially modifiable factors such as performing logistic roles on deployment (aOR (95% CI) 1.13 (1.01 to 1.27)), dissatisfaction with work experience on deployment such as working with colleagues who did not do what was expected of them (aOR (95% CI) 4.09 (3.61 to 4.64)), and major problems at home while deployed (aOR (95% CI) 1.50 (1.38 to 1.63)) were also associated with reporting low unit cohesion. CONCLUSIONS: This is the first study to identify demographic, military service and deployment factors associated with low unit cohesion. The modifiable nature of unit cohesion means that military leaders could use this information to identify subgroups for targeted resilience interventions that may reduce vulnerabilities to mental health problems and improve the job satisfaction, preparedness and deployment experiences of serving members.

Time-course of PTSD symptoms in the Australian Defence Force: a retrospective cohort study.

AIMS: Understanding the time-course of post-traumatic stress disorder (PTSD), and the underlying events, may help to identify those most at risk, and anticipate the number of individuals likely to be diagnosed after exposure to traumatic events. METHOD: Data from two health surveys were combined to create a cohort of 1119 Australian military personnel who deployed to the Middle East between 2000 and 2009. Changes in PTSD Checklist Civilian Version (PCL-C) scores and the reporting of stressful events between the two self-reported surveys were assessed. Logistic regression was used to examine the association between the number of stressful events reported and PTSD symptoms, and assess whether those who reported new stressful events between the two surveys, were also more likely to report older events. We also assessed, using linear regression, whether higher scores on the Kessler Psychological Distress Scale or the Alcohol Use Disorder Identification Test were associated with subsequent increases in the PCL-C in those who had experienced a stressful event, but who initially had few PTSD symptoms. RESULTS: Overall, the mean PCL-C scores in the two surveys were similar, and 78% of responders stayed in the same PCL-C category. Only a small percentage moved from having few symptoms of PTSD (PCL-C < 30) in Survey 1 to meeting the criteria for PTSD (PCL-C ≥ 50) at Survey 2 (1% of all responders, 16% of those with PCL-C ≥ 50 at Survey 2). Personnel who reported more stressful lifetime events were more likely to score higher on the PCL-C. Only 51% reported the same stressful event on both surveys. People who reported events occurring between the two surveys were more likely to record events from before the first survey which they had not previously mentioned (OR 1.48, 95% CI (1.17, 1.88), p < 0.001), than those who did not. In people who initially had few PTSD symptoms, a higher level of psychological distress, was significantly associated with higher PCL-C scores a few years later. CONCLUSIONS: The reporting of stressful events varied over time indicating that while the impact of some stressors endure, others may increase or decline in importance. When screening for PTSD, it is important to consider both traumatic experiences on deployment and other stressful life events, as well as other mental health problems among military personnel, even if individuals do not exhibit symptoms of PTSD on an initial assessment.

Investigation of mechanical properties of cryogenically treated music wire.

It has been reported that treating music wire (high carbon steel wire) by cooling to cryogenic temperatures can enhance its mechanical properties with particular reference to those properties important for musical performance. We use such wire for suspending many of the optics in Advanced LIGO, the upgrade to LIGO­the Laser Interferometric Gravitational-Wave Observatory. Two properties that particularly interest us are mechanical loss and breaking strength. A decrease in mechanical loss would directly reduce the thermal noise associated with the suspension, thus enhancing the noise performance of mirror suspensions within the detector. An increase in strength could allow thinner wire to be safely used, which would enhance the dilution factor of the suspension, again leading to lower suspension thermal noise. In this article, we describe the results of an investigation into some of the mechanical properties of music wire, comparing untreated wire with the same wire which has been cryogenically treated. For the samples we studied, we conclude that there is no significant difference in the properties of interest for application in gravitational wave detectors.

Age-specific measles mortality during the late 19th-early 20th centuries.

Measles mortality fell prior to the introduction of vaccines or antibiotics. By examining historical mortality reports we sought to determine how much measles mortality was due to epidemiological factors such as isolation from major population centres or increased age at time of infection. Age-specific records were available from Aberdeen; Scotland; New Zealand and the states of Australia at the end of the 19th and beginning of the 20th centuries. Despite the relative isolation of Australia, measles mortality was concentrated in very young children similar to Aberdeen. In the more isolated states of Tasmania, Western Australia and Queensland adults made up 14-15% of measles deaths as opposed to 8-9% in Victoria, South Australia and New South Wales. Mortality in Iceland and Faroe Islands during the 1846 measles epidemic was used as an example of islands isolated from respiratory pathogens. The transition from crisis mortality across all ages to deaths concentrated in young children occurred prior to the earliest age-specific mortality data collected. Factors in addition to adult age of infection and epidemiological isolation such as nutritional status and viral virulence may have contributed to measles mortality outcomes a century ago.

Spatio-temporal investigation of the 1918 influenza pandemic in military populations indicates two different viruses.

There were multiple waves of influenza-like illness in 1918, the last of which resulted in a highly lethal pandemic killing 50 million people. It is difficult to study the initial waves of influenza-like illness in early 1918 because few deaths resulted and few morbidity records exist. Using extant military mortality records, we constructed mortality maps based on location of burial in France and Belgium in the British Army, and on home town in Vermont and New York in the USA Army. Differences between early and more lethal later waves in late 1918 were consistent with historical descriptions in France. The maps of Vermont and New York support the hypothesis that previous exposure may have conferred a degree of protection against subsequent infections; soldiers from rural areas, which were likely to have experienced less mixing than soldiers from urban areas, were at higher risk of mortality. Differences between combat and disease mortality in 1918 were consistent with limited influenza virus circulation during the early 1918 wave. We suggest that it is likely that more than one influenza virus was circulating in 1918, which might help explain the higher mortality rates in those unlikely to have been infected in early 1918.

Will improving access to dental care improve oral health-related quality of life?

BACKGROUND: The aim of this study was to determine if Australian Defence Force (ADF) members had better oral health-related quality of life (OHRQoL) than the general Australian population and whether the difference was due to better access to dental care. METHODS: The OHRQoL, as measured by OHIP-14 summary indicators, of participants from the Defence Deployed Solomon Islands (SI) Health Study and the National Survey of Adult Oral Health 2004-06 (NSAOH) were compared. The SI sample was age/gender status-adjusted to match that of the NSAOH sample which was age/gender/regional location weighted to that of the Australian population. RESULTS: NSAOH respondents with good access to dental care had lower OHIP-14 summary measures [frequency of impacts 8.5% (95% CI = 5.4, 11.6), extent mean = 0.16 (0.11, 0.22), severity mean = 5.0 (4.4, 5.6)] than the total NSAOH sample [frequency 18.6 (16.6, 20.7); extent 0.52 (0.44, 0.59); severity 7.6 (7.1, 8.1)]. The NSAOH respondents with both good access to dental care and self-reported good general health did not have as low OHIP-14 summary scores as in the SI sample [frequency 2.6 (1.2, 5.4), extent 0.05 (0.01, 0.10); severity 2.6 (1.9, 3.4)]. CONCLUSIONS: ADF members had better OHRQoL than the general Australian population, even those with good access to dental care and self-reported good general health.

Spatiotemporal patterns of pandemic influenza-related deaths in Allied naval forces during 1918.

This paper draws on the mortality records of the French, US and UK Royal navies to reconstruct the spatiotemporal evolution of the 1918­1919 influenza pandemic in global Allied naval forces. For a total of 7658 deaths attributed to respiratory diseases (French and US navies) and all diseases (UK Royal Navy) at 514 locations worldwide, techniques of spatial point pattern analysis were used to generate weekly maps of global mortality intensity in 1918. The map sequence for the main period of pandemic mortality, mid-August to mid-November 1918, revealed a near-simultaneous development of mutiple foci of high disease intensity in three distant locations (Europe, North America, West Africa). Given the relatively slow speed of naval ships in convoy at this time (<12 knots), our findings suggest that the pandemic influenza virus was circulating on three continents at the observed onset of the main mortality wave.